A high frequency of donations by some blood donors has prompted concern about iron depletion. Five hundred sixteen female and 505 male donors were examined by measurements of hemoglobin, hematocrit, plasma iron, total iron-binding capacity, and ferritin values and detailed histories of iron ingestion, pregnancy and menstrual status, and past blood donations. Hemoglobin, hematocrit, and serum iron studies, unlike ferritin values, were not sensitive indicators of body iron depletion. Reduced iron stores were found in 8% of male and 23% of female donors. Menstruation significantly lowered iron stores in women. The total number of lifetime donations was not as predictive of decreased iron stores as frequency of donations per year. Even casual iron supplementation reduced the impact of donations on iron stores. Administration of iron to donors, especially menstruating women, should be studied by blood programs.